ABSTRACT
BACKGROUND: Orthodenticle homeobox 1 (OTX1) is a transcription factor that plays an important role in various human cancers. However, the function of OTX1 in laryngeal squamous cell carcinoma (LSCC) is largely unknown. We aimed to explore the roles of OTX1 in LSCC and its possible molecular mechanism. METHODS: The expression levels of OTX1 were assessed in LSCC cell lines and tissue samples. We further examined the effect of OTX1 on LSCC progression. The upstream regulator of OTX1 was identified using a computer algorithm and confirmed experimentally. RESULTS: OTX1 was highly expressed in 70.7% (70/99) of LSCC tissue samples. The OTX1 expression in LSCC was significantly correlated with lymph node metastasis. High OTX1 expression in patients with LSCC was correlated with poor prognosis. Knockdown of OTX1 inhibited proliferation, colony formation, migration and invasion in LSCC cells. Knockdown of OTX1 inhibited tumor growth in a xenograft mouse model. Mechanistically, OTX1 might act as a direct target of miR-129-5p. OTX1 enhanced tumorigenicity and tumor growth both in vitro and in vivo. CONCLUSIONS: Our findings support that OTX1 is an oncogene in LSCC tumorigenesis and progression. Furthermore, OTX1 is a direct target of miR-129-5p in LSCC cells. Taken together, OTX1 is a promising diagnostic and therapeutic marker for LSCC.
Subject(s)
Biomarkers, Tumor/genetics , Laryngeal Neoplasms/genetics , MicroRNAs/metabolism , Otx Transcription Factors/genetics , Squamous Cell Carcinoma of Head and Neck/genetics , Animals , Carcinogenesis/genetics , Cell Line, Tumor , Cell Proliferation/genetics , Disease Progression , Female , Follow-Up Studies , Gene Expression Regulation, Neoplastic , Gene Knockdown Techniques , Humans , Kaplan-Meier Estimate , Laryngeal Neoplasms/diagnosis , Laryngeal Neoplasms/mortality , Laryngeal Neoplasms/surgery , Laryngectomy , Larynx/pathology , Larynx/surgery , Male , Mice , Middle Aged , Retrospective Studies , Squamous Cell Carcinoma of Head and Neck/diagnosis , Squamous Cell Carcinoma of Head and Neck/mortality , Squamous Cell Carcinoma of Head and Neck/surgery , Xenograft Model Antitumor AssaysABSTRACT
BACKGROUND: Neutrophil-lymphocyte ratio (NLR) has been shown to be associated with prognosis in various solid tumors. This study aimed to evaluate the prognostic role of NLR in patients with laryngeal squamous cell carcinoma (LSCC). METHODS: A total of 141 LSCC patients were retrospectively reviewed. Patients' demographics were analyzed along with clinical and pathologic data. The optimal cutoff value of NLR was determined using receiver operating characteristic (ROC) curve analysis. The impact of the NLR and other potential prognostic factors on disease-free survival (DFS) and overall survival (OS) was assessed using the Kaplan-Meier method and multivariate Cox regression analysis. RESULTS: The optimal cutoff value of the NLR was 2.17. In the NLR ≤ 2.17 group, the 1-, 3-, and 5-year DFS rates were 88.2, 73.9 and 69.1 %, respectively, while in the NLR > 2.17 group, the DFS rates were 83.0, 54.6 and 49.2 %, respectively. Correspondingly, the 1-, 3-, and 5-year OS rates were 98.9, 85.1 and 77.4 % in the NLR ≤ 2.17 group and 97.9, 63.8 and 53.3 % in the NLR > 2.17 group, respectively. The multivariate Cox proportional hazard model analysis showed that NLR > 2.17 was a prognostic factor for both DFS [hazard ratio (HR) = 1.869; 95 % confidence interval (CI) 1.078-3.243; P = 0.026] and OS (HR =2.177; 95 % CI 1.208-3.924; P = 0.010). CONCLUSION: Our results showed that elevated preoperative NLR was an independent predictor of poor prognosis for patients with LSCC after surgical resection.
Subject(s)
Carcinoma, Squamous Cell/pathology , Laryngeal Neoplasms/pathology , Lymphocytes/pathology , Neutrophils/pathology , Adult , Aged , Aged, 80 and over , Carcinoma, Squamous Cell/mortality , Carcinoma, Squamous Cell/surgery , China/epidemiology , Female , Humans , Laryngeal Neoplasms/mortality , Laryngeal Neoplasms/surgery , Male , Middle Aged , Preoperative Period , Prognosis , ROC Curve , Retrospective Studies , Survival Rate/trendsABSTRACT
OBJECTIVE: To study the value of a new measurement that divided obstructive sleep apnea-hypopnea syndrome (OSAHS) into rapid-eye-movement (REM) related and non-rapid-eye-movement (NREM) related subgroups. METHODS: According to Siddiqui classification, 137 adult patients with OSHAS were diagnosed as REM-related OSAHS [REM apnea hypopnea index (AHI)/NREM AHI > 1] or NREM-related OSAHS (REM AHI/NREM AHI < 1). Polysomnographic data were compared and discussed. RESULTS: (1) There were 72 cases defined as REM-related OSAHS (52.6%) and 65 cases defined as NREM-related OSAHS (47.4%). (2) In all cases, total AHI and NREM AHI in REM-related OSAHS were significantly lower than those in NREM-related OSAHS, while lowest arterial oxygen saturation (LSaO2), REM LSaO2 and NREM LSaO2 were significantly higher than those in NREM-related OSAHS (t were -6.466, -7.638, 3.426, 2.472, 4.873 respectively, P < 0.05). No significance was found in sleep structure, REM AHI and REM LSaO2 between REM-related and NREM-related OSAHS (P > 0.05). (3) Given the severity of OSHAS, the constituent ratio of REM-related OSAHS decreased (77.8%, 61.5%, 37.3%) from mild to severe OSAHS, while that of NREM-related OSAHS rose (22.7%, 38.5%, 62.7%; chi² = 16.996, P < 0.01). In mild and moderate groups, REM LSaO2 of REM-related OSAHS was significantly lower than those in NREM-related OSAHS (t were -4.273 and -2.136, P < 0.05), while the differences of total AHI and LSaO2, NREM LSaO2 between these two types were not significant. In severe group, AHI in NREM-related OSAHS was significantly higher than that in REM-related OSAHS, while LSaO2, REM LSaO2 and NREM LSaO2 was significantly lower than those in REM-related OASHS (t were -4.943, 2.574, 1.996, 3.571, P ≤ 0.05). (4) There was no significance in sleeping latency and efficiency between REM-related and NREM-related OSHAS. CONCLUSIONS: REM-related OSHAS mainly exists in mild and moderate OSHAS, while NREM-related one mainly exists in severe OSHAS. NREM-related OSAHS may be more severe in AHI and hypoxia than REM-related one. Whenever obstructive apnea happened in REM or NREM period, its impacts on sleep structure, efficiency and latency have no difference.